Efficient Glycosylation Using ODS Adsorption Method Based on the Affinity of Long Alkoxybenzyl Glycoside

Abstract

p-Oleyloxybenzyl (POB) glycoside, selectively removable with TMSOTf, was developed as a protecting group for the glycosyl acceptor. Activation of the trichloroacetimidate was efficiently accomplished using 20 mol% of Cu(OTf)₂. Purification of the resulting glycoside was rapidly and efficiently accomplished by an ODS adsorption method based on the significant affinity of long alkyl chains and the ODS. The procedure is particularly useful for convergent oligosaccharide synthesis.

Key words

glycosylations - glycosides - octadecylsilane - p-oleyl­oxybenzyl ether - ODS adsorption

References and Notes

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11

Synthesis of Trisaccharide 8 Using an ODS Adsorption Method - General Procedure
To a stirred suspension of Cu(OTf)₂ (30 mg, 0.084 mmol) and 4 Å MS (powder, 50 mg) in anhyd CH₂Cl₂ (3 mL) was added a solution of diol 6 (300 mg, 0.42 mmol) at r.t., and the mixture was stirred for 20 min. To this was added a solution of trichloroacetimidate 7 (936 mg, 1.47 mmol) in CH₂Cl₂ (3 mL) using a syringe drive over a period of 1 h, and the mixture was stirred for 12 h at the same temperature. The reaction was terminated by the addition of Et₃N (720 mg, 7.12 mmol). Insoluble material was removed by passing through a cotton Celite pad, and the filtrate was concentrated under reduced pressure. The resulting material was dissolved in MeCN (100 mL) and adsorbed onto an ODS column (20 g), and the polar byproducts were eluted with MeCN (100 mL). Trisaccharide 8 (666 mg, 95% yield) was recovered by the elution with CH₂Cl₂.
Compound 8: [α]_D ^²² +41.5 (c 1.9, CHCl₃). FT-IR (neat): 3087, 3062, 3004, 2925, 2855, 1951, 1878, 1809, 1745, 1611, 1585, 1511, 1496, 1454, 1368, 1285, 1237, 1132, 1101, 1050, 1026, 981, 913, 840, 736, 699, 604 cm^-¹. ^¹H NMR (400 MHz, CDCl₃): δ = 0.89 (3 H, t, J = 6.8 Hz), 1.27-1.46 (22 H, m), 1.74-1.81 (2 H, m), 2.01-2.07 (4 H, m), 2.09 (3 H, s), 2.17 (3 H, s), 3.61-3.70 (3 H, m), 3.73-3.78 (2 H, m), 3.82-3.95 (11 H, m), 3.99 (1 H, dd, J = 9.2, 3.2 Hz), 4.03 (1 H, dd, J = 9.2, 3.2 Hz), 4.19 (1 H, dd, J = 9.6, 3.2 Hz), 4.31 (1 H, d, J = 11.6 Hz), 4.41-4.70 (12 H, m), 4.54 (1 H, d, J = 11.6 Hz), 4.76 (1 H, d, J = 11.2 Hz), 4.83 (1 H, d, J = 1.6 Hz), 4.88 (2 H, dd, J = 10.8, 3.2 Hz), 4.98 (1 H, d, J = 2.0 Hz), 5.20 (1 H, d, J = 1.6 Hz), 5.33-5.41 (2 H, m), 5.50-5.52 (2 H, m), 6.75-6.78 (2 H, m), 7.12-7.35 (42 H, m). ^¹³C NMR (100 MHz, CDCl₃): δ = 14.4 (q), 21.3 (q), 21.5 (q), 22.3 (t), 26.3 (t), 27.4 (t), 29.5-30.0 (many t), 32.2 (t), 32.9 (t), 66.7 (t), 68.2 (t), 68.7 (d, 2 C), 68.9 (t), 69.0 (d), 69.2 (t), 71.5 (d), 71.6 (d, 2 C), 72.0 (t), 72.4 (d), 72.4 (t), 73.6 (t), 73.6 (t), 74.4 (d), 74.5 (d), 75.2 (t), 75.3 (d), 75.4 (t), 77.5 (d), 77.8 (d), 77.9 (d), 78.3 (d), 79.0 (d), 95.7 (d), 98.2 (d), 99.9 (d), 114.6 (d), 127.7-130.2 (many d), 138.0 (s), 138.1 (s), 138.1 (s), 138.3 (s), 138.5 (s), 138.5 (s), 138.8 (s), 138.9 (s), 159.0 (s), 170.4 (s), 170.6 (s). MS (FAB, m-NBA): m/z = 1689 [M + Na]⁺. HRMS (FAB): m/z calcd for C₁₀₃H₁₂₄O₁₉Na [M + Na]⁺: 1687.8635; found: 1687.8654.

12

No other products were detected in the ^¹³C NMR spectrum of the saccharide.

13

In the reaction using 2-acetylated trichloroacetimidate as glycosyl donor, an ortho ester such as 22 was produced as an intermediate. By continuing treatment with Cu(OTf)₂ (12 h), the ortho ester was transformed to the desired glycoside (Figure  [²] ).

14

The anomeric stereochemistry of 12 was determined from the coupling constants J _CH for anomeric carbons (164 Hz). Although the β-isomer was separable using HPLC, it was not possible to determine the stereochemistry by NMR spectroscopy due to insufficient sample. However, as the high-resolution mass spectrum suggested the structure of a tetrasaccharide, we concluded the stereochemistry is β.

15

Compound 16 was prepared in 96% yield from the disaccharide 19 by treatment with HF˙pyridine.